Tuberculous meningitis is a cerebrovascular disease caused by Mycobacterium tuberculosis. The incidence of tuberculous meningitis has been gradually increasing in recent years, and its causes are not very clear, and it is estimated that it may be related to environmental pollution. Typical cases are relatively easy to diagnose, but there are many atypical cases, which cause serious sequelae and even affect the patient’s life if treatment is delayed.
Brief introduction
Tuberculous meningitis is one of the most important types of pediatric tuberculosis and usually develops within 3 months to 1 year after the primary tuberculosis infection, mostly in children aged 1 to 3 years. The course of tuberculous meningitis from onset to death is about 3-6 weeks.
～It is the most important cause of pediatric TB death. Before the introduction of anti-tuberculosis drugs, the mortality rate was almost 100%. Since BCG vaccination and tuberculosis prevention and control have been widely promoted in China, the incidence of this disease has decreased significantly compared with the past, and the prognosis has improved greatly, and most cases can be cured if diagnosed early and treated reasonably early. However, if the diagnosis is not timely and the treatment is not appropriate, the mortality rate and the incidence of sequelae are still high. Therefore, early diagnosis and reasonable treatment are the keys to improve the prognosis of this disease. Dong Xiaowei, Department of Tuberculosis Medicine, Heilongjiang Tuberculosis Hospital
Pathogenesis
According to domestic data, among 1180 cases of tuberculous meningitis, 44.2% of them were diagnosed with corniform tuberculosis. 143 cases (94%) of 152 cases of tuberculous meningitis were found to have tuberculosis of other organs of the body and 142 cases (93.4%) were combined with pulmonary tuberculosis, of which corniform tuberculosis was the first. Among them, the first one was the cornified tuberculosis.
When the primary tuberculosis lesion becomes established, the tubercle bacilli in the lesion can stay in the meninges, brain parenchyma and spinal cord through blood flow, forming hidden tuberculosis lesions, including tuberculosis nodules and tuberculoma. When the above lesions once break down. The tuberculosis bacilli directly enter the subarachnoid space, causing tuberculous inflammation. In addition, tuberculous lesions in tissues near the brain such as the middle ear, mastoid process, cervical spine, and skull can also spread directly and invade the meninges, but this is less common.
The occurrence of tuberculous meningitis is associated with a high degree of hypersensitivity of the body patch at the time of the primary tuberculosis. From the pathogenesis point of view, tuberculous meningitis is secondary to tuberculosis, therefore, attention should be paid to finding the primary lesion. However, there are a few cases where the primary lesion has healed or cannot be found, and in such cases, vigilance should be increased to avoid misdiagnosis.
Pathological typing
1. plasma type
2. cerebral hypoencephalitis type
3. meningoencephalitis type
4. tuberculous spinal soft and hard meningitis type
Clinical manifestations
Tuberculous meningitis often has a slow onset, but there are also sudden onset cases.
(a) The clinical manifestations of typical tuberculous meningitis can be divided into three stages
1. prodromal phase (early) about 1 to 2 weeks
Generally, the onset of the disease is slow, based on the original tuberculosis, there is a change in temperament, such as irritability, irritability, crying, or mental lethargy, dullness, drowsiness or sleeplessness, staring, loss of appetite, emaciation, and low fever, constipation or unexplained recurrent vomiting. Older children may complain of headache, which may be intermittent at first and then persistent. Infants and young children show frowning, hitting the head with hands, crying, etc.
2. Meningeal irritation period (middle period) about 1 to 2 weeks
The main manifestations are meningitis and increased intracranial pressure. Low fever, increasing headache may be persistent. Vomiting is frequent, often in the form of jets, there may be sensory hypersensitivity, and drowsiness and disorders of consciousness may appear from time to time. Typical meningeal irritation is usually seen in older children, while infants mainly show a full or bulging fontanelle, loss of abdominal wall reflexes and hyperactive tendon reflexes. If the disease continues to progress, the infant will enter a coma and may have convulsive episodes. The most common symptoms of cranial nerve involvement are facial nerve, ophthalmic nerve and abducens nerve paresis, mostly unilateral, manifested by loss of nasolabial fold, drooping eyelid, exophthalmia, diplopia and dilated pupil.
3. Late stage (coma phase) about 1 to 2 weeks
The consciousness disorder is aggravated by repeated convulsions, and the consciousness goes into semi-coma or coma, with dilated pupils, loss of light reflex, irregular respiratory rhythm and even tidal breathing or apnea. There is often metabolic acidosis, cerebral sodium iron loss syndrome, hypokalemia and other disorders of water and electrolyte metabolism. Finally, the body temperature may rise to more than 40℃, and eventually death is caused by respiratory and circulatory failure.
(B) Atypical tuberculous meningitis
1. In older children with tuberculous meningitis, the brain parenchyma is often suddenly ruptured due to hidden lesions. A large number of tuberculosis bacilli invade the cerebrospinal tract causing an acute reaction of the meninges. The onset of the disease is rapid, with sudden fever, convulsions, and obvious signs of meningeal irritation, but there may be no obvious tuberculosis lesions in the lungs or other areas; the peripheral blood picture has an increased total leukocyte count and neutrophil percentage; the cerebrospinal tract is mildly cloudy, and the leukocyte count may be ≥1×109/L (1000/mm3) with neutrophils in the majority, which is easily misdiagnosed as septic meningitis.
2. Sometimes it shows signs of persistent increase in intracranial pressure, hypothermia, progressive headache, and gradually increasing jet vomiting. The cerebrospinal fluid pressure is increased, leukocytes are mildly increased, protein is increased, sugar is decreased, and chloride is normal. Brain ultrasonography indicates ventricular dilatation or midline displacement, and brain scan shows radiotracer-intense areas, which can be easily misdiagnosed as brain abscess or brain tumor.
3. If the disease is caused by the spread of middle ear or mastoid nodules, it often starts with fever, ear pain and vomiting, and is easily misdiagnosed as acute otitis media, and is easily misdiagnosed as otitis media combined with cerebral chemistry when meningeal irritation signs are present, or as brain abscess when limited neurological localization signs are present.
4. In infants under six months of age with generalized hematogenous tuberculosis, nodular brain may develop secondary to or simultaneously with nodular brain, fever, enlarged liver and spleen lymph nodes, and may be accompanied by skin rash, but chest radiographs may reveal corniform tuberculosis.
Diagnosis and differential diagnosis
Early diagnosis of pediatric tuberculous meningitis is a prerequisite for early and reasonable treatment.
～Therefore, the timely and reasonable diagnosis and treatment is the key to the disease.
(A) Diagnosis basis
1. Medical history and clinical manifestations
Early diagnosis relies on detailed history, thorough clinical observation, and a high degree of vigilance for the disease. The possibility of the disease should be considered in children with primary pulmonary tuberculosis or cornual tuberculosis who present with symptoms of obscure causes, especially fever and vomiting after measles or whooping cough. In other cases, if the child has vomiting with no obvious cause, change in temperament, headache, neck resistance, and persistent fever that is not effective with general anti-infection, the child should be asked if there is any history of tuberculosis contact and previous history of tuberculosis, and if tuberculous meningitis is suspected, cerebrospinal fluid examination should be performed.
X-ray examination The number of children with tuberculosis lesions in the lungs of children with nodular brain is about 42
～The number of children with tuberculosis in the lungs is about 42% to 92%, of which about 44% belong to the cornified type of tuberculosis. Therefore, any suspicion of this disease, should be carried out chest X-ray, such as the detection of tuberculosis in the lungs, especially the corn type of tuberculosis, will help the diagnosis; but the chest X-ray is normal, can not be denied nodular brain.
3. Cerebrospinal fluid examination
(1) Routine examination
In tuberculous meningitis, the pressure of cerebrospinal fluid is increased, and the appearance is clear or glassy or slightly cloudy, and the cell count is generally increased. However, the cell count may be normal early in the disease. Protein quantification increases, mostly above 0.4g/L, generally 1 to 3g/L. If it is more than 3g/L, it should be considered as pearl retinal adhesions or even spinal canal obstruction. Sugar quantification may be normal in the early stage and gradually decrease later. Cerebrospinal fluid sugar content is reduced. The chloride content is often reduced.
The simultaneous decrease in sugar and chloride is typical of tuberculous meningitis. After 12 to 24 hours of placing meningeal fluid in an upright small test tube, a gauze curtain-like film may be formed, with this film or cerebrospinal fluid precipitation by antacid staining or using direct fluorescent antibody method can find Mycobacterium tuberculosis.
(2) Lymphocyte transformation test
The lymphocyte conversion of cerebrospinal fluid can be measured by 3H-TdR participation method. In tuberculous meningitis, the lymphocyte conversion rate of cerebrospinal fluid increases significantly under the stimulation of PPD, which has early assertion value.
(3) Immunoglobulin determination
Immunoglobulin measurement of cerebrospinal fluid has some significance for the differential diagnosis of meningitis. IgG is predominantly increased in cerebrospinal fluid in nodular brain, IgG and IgM are increased in chemobrain, and IgG is mildly increased in viral brain.IgM is not increased.
(4) Lactate and lactate dehydrogenase measurement
Lysozyme index determination and cerebrospinal fluid anti-tuberculosis antibody test. Cerebrospinal fluid PCR method to detect tuberculosis antigen, etc.
4. Other tests
(1) Positive tuberculin test is helpful for diagnosis, but a negative result cannot exclude the disease.
(2) Fundus examination reveals tuberculosis nodules on the choroid. Cerebrospinal fluid changes can be definitely concluded.
(3) Peripheral blood picture shows elevated total leukocyte count and neutrophil ratio. Mild anemia. Blood pressure is increased, but there are also normal cases.
(B) Differential diagnosis
Tuberculous meningitis must be differentiated from the following diseases.
1. septic meningitis
2. viral meningoencephalitis
3. novel cryptococcal meningitis
Treatment
(A) General treatment
Early cases should be hospitalized, bed rest, supply nutritious food with high vitamin (A, D, C) and high protein, nasal feeding for coma, if you can swallow, you can try to feed by. The room should be regularly ventilated and disinfected, and the air in the room should be fresh and well-lit. Pay attention to eye, nose and mouth care, turning, and prevent the occurrence of hemorrhoids and pulmonary stasis.
(B) Anti-tuberculosis treatment
Anti-tuberculosis drugs should be selected as bactericidal agents with strong penetration and high cerebrospinal fluid concentration, and toxic side effects should be observed during treatment to avoid the combination of drugs with the same toxic side effects as far as possible. Currently, the commonly used therapeutic drugs are isoniazid, streptomycin and ethambutol, para-aminosalicylic acid, rifampin, pyrazinamide, etc.
(C) Application of adrenocorticosteroids
Adrenocorticotropic hormone can inhibit the inflammatory reaction and has the effect of anti-fibrous tissue formation; it can reduce endarteritis, thus rapidly reducing the symptoms of poisoning and meningeal irritation signs; it can lower the brain pressure, reduce cerebral edema and prevent the obstruction of the spinal canal. It is an effective adjunctive therapy to anti-tuberculosis drugs. Generally early application is more effective. Prednisone can be used 1~2mg/kg per day orally for 6~12 weeks, and the drug can be gradually reduced and stopped 4~6 weeks after the condition improves. Or use dexamethasone 0.25-1mg/kg per day in tranquilization. In the acute stage, hydrocodisone can be used 5
～In the acute stage, hydrocodone can be used at 5~10mg/kg per day for 3~5 days and then changed to prednisone orally.
(iv) Symptomatic treatment
1. Increased cerebral pressure
(1) 20% mannitol 5-10ml/kg rapid intravenous injection, if necessary, once every 4-6 hours, 50% glucose 2-4ml/kg sedation, alternating with mannitol.
(2) Acetazolamide 20-40mg/kg/day in 2-3 doses for 3 days and stop for 4 days.
(3) If necessary, ventricular puncture and drainage, not more than 200ml per day for 2-3 weeks.
2. Hyperthermia, convulsions Treat as after.
3. Due to vomiting, insufficient intake, cerebral hyponatremia should be replenished with the required water and sodium.
(E) Intrathecal medication
In advanced and severe cases with high cerebral pressure, severe hydrocephalus, obstruction of the spinal canal and persistent decrease of cerebrospinal fluid sugar or persistent increase of protein, intrathecal injection can be considered.
(F) Precautions
1, improper timing
Tuberculous meningitis must be treated early, as long as tuberculous meningitis cannot be ruled out, it should not be misdiagnosed due to atypical clinical manifestations and atypical cerebrospinal fluid, thus losing the best time for cure. According to statistics: the first week to start anti-tuberculosis treatment, 70% remission; the second week to start anti-tuberculosis treatment, 50% remission; more than 3 weeks before anti-tuberculosis treatment, the efficacy is extremely poor, and the mortality rate is extremely high.
2, no combination of drugs, insufficient course of treatment
The principle of combined medication: the first choice of bactericidal drugs, with antibacterial drugs, WHO recommends the selection of at least three kinds of drugs
Combination therapy, commonly used isoniazid, rifampin and pyrazinamide. At present, the main first-line anti-tuberculosis drugs are recommended.
3.Whether to apply hormone reasonably
For severe tuberculous meningitis, a certain amount of hormone is applied in a short course in the early stage, which can reduce exudation and cerebral edema, and can be injected intrathecally if necessary to prevent complications. According to statistics, the survival rate: 45% with hormones, 25% without hormones, and a course of 6-8 weeks is appropriate.
4, whether to deal with complications in a timely manner
There are many complications of tuberculous meningitis, such as hydrocephalus, cerebrospinal arachnoiditis, tuberculoma and so on. If not treated in a timely manner, it will definitely affect the efficacy of treatment.
5.Whether there is mixed infection
If TB meningitis is accompanied by bacterial and viral infections, failure to detect and treat them in a timely manner can make treatment difficult, so clinicians must be highly aware of them.
6. Presence of tuberculosis foci in other parts of the body
The presence of tuberculosis foci in other parts of the body makes treatment difficult.
7. Presence of underlying diseases
The presence of autoimmune disorders, HIV infection, tumors, etc. can also make treatment difficult.
8.Individual differences
Due to individual differences, the sensitivity to anti-tuberculosis drugs is different, which inevitably affects the efficacy.
Prognosis of tuberculous meningitis
In recent years, the prognosis of tuberculous meningitis has greatly improved due to the improvement of diagnostic methods and the development and continuous improvement of chemotherapy regimens. Early and reasonable treatment can lead to complete cure. The criteria for cure are: (1) complete disappearance of clinical symptoms and signs, and no sequelae. ②The cerebrospinal fluid examination is normal. ③No recurrence after two years of follow-up observation after the course of treatment. If the diagnosis is not timely, the treatment is not reasonable, or the child is too young, the lesion is too serious, etc., there is still a high (15
～(15~36%) of death rate. If recurrence is found during the course of treatment follow-up, the prognosis can still be improved with reasonable treatment.